AU2005307704A1 - Novel 2H-chromene derivatives as selective estrogen receptor modulators - Google Patents
Novel 2H-chromene derivatives as selective estrogen receptor modulators Download PDFInfo
- Publication number
- AU2005307704A1 AU2005307704A1 AU2005307704A AU2005307704A AU2005307704A1 AU 2005307704 A1 AU2005307704 A1 AU 2005307704A1 AU 2005307704 A AU2005307704 A AU 2005307704A AU 2005307704 A AU2005307704 A AU 2005307704A AU 2005307704 A1 AU2005307704 A1 AU 2005307704A1
- Authority
- AU
- Australia
- Prior art keywords
- group
- alkyl
- chromen
- ethoxy
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 125000000850 2H-chromenyl group Chemical class O1C(C=CC2=CC=CC=C12)* 0.000 title abstract 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 title description 7
- 229940095743 selective estrogen receptor modulator Drugs 0.000 title description 6
- 238000000034 method Methods 0.000 claims abstract description 46
- 238000002360 preparation method Methods 0.000 claims abstract description 38
- 102000015694 estrogen receptors Human genes 0.000 claims abstract description 24
- 108010038795 estrogen receptors Proteins 0.000 claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
- 208000035475 disorder Diseases 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 230000001404 mediated effect Effects 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 150
- 239000000203 mixture Substances 0.000 claims description 42
- -1 carboxy, amino Chemical group 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 22
- 229940011871 estrogen Drugs 0.000 claims description 19
- 239000000262 estrogen Substances 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 229910003849 O-Si Inorganic materials 0.000 claims description 12
- 229910003872 O—Si Inorganic materials 0.000 claims description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
- 239000000583 progesterone congener Substances 0.000 claims description 12
- 208000001132 Osteoporosis Diseases 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 210000001519 tissue Anatomy 0.000 claims description 11
- 206010060800 Hot flush Diseases 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 206010047791 Vulvovaginal dryness Diseases 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 201000009273 Endometriosis Diseases 0.000 claims description 8
- 230000003920 cognitive function Effects 0.000 claims description 8
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
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- 206010020718 hyperplasia Diseases 0.000 claims description 7
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- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
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- 102000005962 receptors Human genes 0.000 claims description 6
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- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
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- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- ZAOFBTDRLXTTRR-UHFFFAOYSA-N 4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(C)=CC1C(C=C1)=CC=C1OCCN1CCCCC1 ZAOFBTDRLXTTRR-UHFFFAOYSA-N 0.000 claims description 3
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- BCAHYKSCCYDNLZ-UHFFFAOYSA-N 3-(hydroxymethyl)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(C)=C(CO)C1C(C=C1)=CC=C1OCCN1CCCCC1 BCAHYKSCCYDNLZ-UHFFFAOYSA-N 0.000 claims description 2
- FANGYSXRPPSHRV-UHFFFAOYSA-N 4-(2-hydroxyethyl)-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(CCO)=CC1C(C=C1)=CC=C1OCCN1CCCCC1 FANGYSXRPPSHRV-UHFFFAOYSA-N 0.000 claims description 2
- QYHKGMAAOCANDP-UHFFFAOYSA-N 6-[4-[2-(dimethylamino)ethoxy]phenyl]-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-ol Chemical compound C1=CC(OCCN(C)C)=CC=C1C1C(CCCCC2)=C2C2=CC=C(O)C=C2O1 QYHKGMAAOCANDP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000002785 azepinyl group Chemical group 0.000 claims description 2
- 238000011262 co‐therapy Methods 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 201000006828 endometrial hyperplasia Diseases 0.000 claims 2
- 201000001514 prostate carcinoma Diseases 0.000 claims 2
- PAUMCYOKUFGQRG-GDLZYMKVSA-N (2r)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-3-(2-trimethylsilylethoxymethyl)-2h-chromen-7-ol Chemical compound C1=CC([C@@H]2C(COCC[Si](C)(C)C)=C(C3=CC=C(O)C=C3O2)C)=CC=C1OCCN1CCCCC1 PAUMCYOKUFGQRG-GDLZYMKVSA-N 0.000 claims 1
- PAUMCYOKUFGQRG-LJAQVGFWSA-N (2s)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-3-(2-trimethylsilylethoxymethyl)-2h-chromen-7-ol Chemical compound C1=CC([C@H]2C(COCC[Si](C)(C)C)=C(C3=CC=C(O)C=C3O2)C)=CC=C1OCCN1CCCCC1 PAUMCYOKUFGQRG-LJAQVGFWSA-N 0.000 claims 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000003870 2-(1-piperidinyl)ethoxy group Chemical group [*]OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- SXENAAYLHGRIAZ-UHFFFAOYSA-N 4-cyclopentyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound O1C2=CC(O)=CC=C2C(C2CCCC2)=CC1C(C=C1)=CC=C1OCCN1CCCCC1 SXENAAYLHGRIAZ-UHFFFAOYSA-N 0.000 claims 1
- IFANTIOZECIHCH-UHFFFAOYSA-N 5-[4-(2-piperidin-1-ylethoxy)phenyl]-1,2,4,5-tetrahydropyrano[3,4-c]chromen-8-ol Chemical compound O1C2=CC(O)=CC=C2C(CCOC2)=C2C1C(C=C1)=CC=C1OCCN1CCCCC1 IFANTIOZECIHCH-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 14
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- 239000012043 crude product Substances 0.000 description 57
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- 239000012044 organic layer Substances 0.000 description 43
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 42
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/18—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted otherwise than in position 3 or 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Endocrinology (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
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- Pregnancy & Childbirth (AREA)
- Urology & Nephrology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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| US60/628,987 | 2004-11-18 | ||
| PCT/US2005/041648 WO2006055694A1 (en) | 2004-11-18 | 2005-11-17 | Novel 2h-chromene derivatives as selective estrogen receptor modulators |
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| AU2005307704A1 true AU2005307704A1 (en) | 2006-05-26 |
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| US20200390755A1 (en) * | 2018-08-01 | 2020-12-17 | Shaanxi Micot Technology Co., Ltd. | Compound for treating nervous system diseases and use thereof |
| CN119176799B (zh) * | 2024-09-19 | 2025-10-03 | 晨伫(杭州)生物科技有限责任公司 | 色烯衍生物及其应用 |
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|---|---|---|---|---|
| US6060503A (en) * | 1991-12-02 | 2000-05-09 | Endorecherche, Inc. | Benzopyran-containing compounds and method for their use |
| DE10013782A1 (de) * | 2000-03-15 | 2001-10-18 | Schering Ag | 4-Fluoralkyl-2H-benzopyrane mit antiestrogener Wirksamkeit, Verfahren zu ihrer Herstellung, pharmazeutische Präparate, die diese enthalten sowie deren Verwendung zur Herstellung von Arzneimitteln |
| IL161325A0 (en) * | 2001-11-19 | 2004-09-27 | Lilly Co Eli | Substituted benzopyrans as selective estrogen receptor-beta agonists |
| US7329654B2 (en) * | 2001-12-19 | 2008-02-12 | Janssen Pharmaceutica N.V. | Heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators |
-
2005
- 2005-11-17 AU AU2005307704A patent/AU2005307704A1/en not_active Abandoned
- 2005-11-17 CN CNA2005800468519A patent/CN101103011A/zh active Pending
- 2005-11-17 ES ES05824228T patent/ES2314747T3/es not_active Expired - Lifetime
- 2005-11-17 SI SI200530558T patent/SI1812417T1/sl unknown
- 2005-11-17 JP JP2007543221A patent/JP2008520688A/ja not_active Withdrawn
- 2005-11-17 PL PL05824228T patent/PL1812417T3/pl unknown
- 2005-11-17 DE DE602005010735T patent/DE602005010735D1/de not_active Expired - Fee Related
- 2005-11-17 US US11/281,074 patent/US20060166933A1/en not_active Abandoned
- 2005-11-17 WO PCT/US2005/041648 patent/WO2006055694A1/en not_active Ceased
- 2005-11-17 PT PT05824228T patent/PT1812417E/pt unknown
- 2005-11-17 CA CA002587669A patent/CA2587669A1/en not_active Abandoned
- 2005-11-17 DK DK05824228T patent/DK1812417T3/da active
- 2005-11-17 AT AT05824228T patent/ATE412643T1/de not_active IP Right Cessation
- 2005-11-17 EP EP05824228A patent/EP1812417B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| PL1812417T3 (pl) | 2009-04-30 |
| SI1812417T1 (sl) | 2009-04-30 |
| EP1812417A1 (en) | 2007-08-01 |
| CA2587669A1 (en) | 2006-05-26 |
| DK1812417T3 (da) | 2009-02-16 |
| DE602005010735D1 (de) | 2008-12-11 |
| WO2006055694A1 (en) | 2006-05-26 |
| JP2008520688A (ja) | 2008-06-19 |
| EP1812417B1 (en) | 2008-10-29 |
| ES2314747T3 (es) | 2009-03-16 |
| US20060166933A1 (en) | 2006-07-27 |
| CN101103011A (zh) | 2008-01-09 |
| ATE412643T1 (de) | 2008-11-15 |
| PT1812417E (pt) | 2008-12-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |